Calibrated photoacoustic spectrometry with an imaging system

Photoacoustic (PA) contrast agents are usually characterized with spectrophotometry or uncalibrated PA imaging systems, leading to partial assessment of their PA efficacy. To perform calibrated PA spectroscopy with a PA imaging system, we developed a method that both corrects for the spectral energy distribution of excitation light and performs a conversion from arbitrary to spectroscopic units, using a reference solution of cupric sulfate. The method was implemented on an imaging setup based on a tunable laser and a 5MHz ultrasound array. We demonstrated robust calibrated spectroscopy on 15$\mu$L sample volumes of known chromophores and commonly used PA contrast agents, and for multiple samples simultaneously. The detection was linear with the absorption and the sensitivity below 0.08cm-1

High-Resolution 1.5-Tesla Magnetic Resonance Imaging for Tissue-Engineered Constructs: A Noninvasive Tool to Assess Three-Dimensional Scaffold Architecture and Cell Seeding

International audienceTissue-engineered scaffolds are made of biocompatible polymers with various structures, allowing cell seeding, growth, and differentiation. Noninvasive imaging methods are needed to study tissue-engineered constructs before and after implantation. Here, we show that high-resolution magnetic resonance imaging (MRI) performed on a clinical 1.5-T device is a reliable technique to assess three-dimensional structures of porous scaffolds and to validate cell-seeding procedures. A high-temperature superconducting detection coil was used to achieve a resolution of 30Â30Â30 mm 3 when imaging the scaffolds. Three types of structures with tuneable architectures were prepared from naturally derived polysaccharides and evaluated as scaffolds for mesenchymal stem cell (MSC) culture. To monitor cell seeding, MSCs were magnetically labeled using simple incubation with anionic citrate-coated iron-oxide nanoparticles for 30 min. Iron uptake was quantified using single-cell magnetophoresis, and cell proliferation was checked for 7 days after labeling. Three-dimensional (3D) microstructures of scaffolds were assessed using MRI, revealing lamellar or globular porous organization according to the scaffold preparation process. MSCs with different iron load (5, 12 and 31 pg of iron per cell) were seeded on scaffolds at low density (132 cells=mm 3) and detected on 3D gradient-echo MR images according to phase distortions and areas of intensely low signal, whose size increased with cell iron load and echo time. Overall signal loss in the scaffold correlated with the number of seeded cells and their iron load. Different organizations of cells were observed depending on the scaffold architecture. After subcutaneous implantation in mice, scaffolds seeded with labeled cells could be distinguished in vivo from scaffold with nonlabeled cells by observation of signal and phase heterogeneities and by measuring the global signal loss. High-resolution 1.5-T MRI combined with efficient intracellular contrast agents shows promise for noninvasive 3D visualization of tissue-engineered constructs before and after in vivo implantation

The one year fate of iron oxide coated gold nanoparticles in mice

Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate

Covalent functionalization of multi-walled carbon nanotubes with a gadolinium chelate for efficient T1-weighted magnetic resonance imaging

Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non-invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non-ionizing whole-body high field magnetic resonance imaging (MRI) is used to follow the distribution of water-dispersible non-toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd-CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd-CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd-CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd-CNTs is observed, confirming the evidences of other studies using different imaging modalities

Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment

Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy

Temperature Dependence of Water Absorption in the Biological Windows and Its Impact on the Performance of Ag2S Luminescent Nanothermometers

The application of nanoparticles in the biological context generally requires their dispersion in aqueous media. In this sense, luminescent nanoparticles are an excellent choice for minimally invasive imaging and local temperature sensing (nanothermometry). For these applications, nanoparticles must operate in the physiological temperature range (25–50 °C) but also in the nearinfrared spectral range (750–1800 nm), which comprises the three biological windows of maximal tissue transparency to photons. In this range, water displays several absorption bands that can strongly affect the optical properties of the nanoparticles. Therefore, a full understanding of the temperature dependence of water absorption in biological windows is of paramount importance for applications based on these optical properties. Herein, the absorption spectrum of water in the biological windows over the 25–65 °C temperature range is systematically analyzed, and its temperature dependence considering the coexistence of two states of water is interpreted. Additionally, to illustrate the importance of state-of-the-art applications, the effects of the absorption of water on the emission spectrum of Ag2S nanoparticles, the most sensitive luminescent nanothermometers for in vivo applications to date, are presented. The spectral shape of the nanoparticles’ emission is drastically affected by the water absorption, impacting their thermometric performanceThis work was financed by the Spanish Ministerio de Ciencia e Innovación under project PID2019-106211RB-I00, by the Instituto de Salud Carlos III (PI19/00565), by the Comunidad Autónoma de Madrid (S2017/BMD3867 RENIM-CM) and co-financed by the European structural and investment fund. Additional funding was provided by the European Union Horizon 2020 FETOpen project NanoTBTech (801305), the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP21_A4 (2021/0427), and by COST action CA17140. A.B. acknowledges funding support through the TALENTO 2019T1/IND14014 contract (Comunidad Autónoma de Madrid). F.E.M. and L.D.C. acknowledge the financial support received from the project Shape of Water (PTDC/NAN-PRO/3881/2020) through Portuguese fund

Intracellular degradation of functionalized carbon nanotube/iron oxide hybrids is modulated by iron via Nrf2 pathway.

The in vivo fate and biodegradability of carbon nanotubes is still a matter of debate despite tremendous applications. In this paper we describe a molecular pathway by which macrophages degrade functionalized multi-walled carbon nanotubes (CNTs) designed for biomedical applications and containing, or not, iron oxide nanoparticles in their inner cavity. Electron microscopy and Raman spectroscopy show that intracellularly-induced structural damages appear more rapidly for iron-free CNTs in comparison to iron-loaded ones, suggesting a role of iron in the degradation mechanism. By comparing the molecular responses of macrophages derived from THP1 monocytes to both types of CNTs, we highlight a molecular mechanism regulated by Nrf2/Bach1 signaling pathways to induce CNT degradation via NOXjournal article2017 Jan 252017 01 25importe

Whither Magnetic Hyperthermia? A Tentative Roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02)

Nanoparticules magnétiques au cœur des cellules : des outils pour les thérapies cellulaires

Les nanotechnologies ont fait leur entrée dans le vivant et sont en passe de révolutionner la médecine de demain. Par une  « convergence d’échelle » , ces dispositifs de taille nanométrique s’insèrent au cœur des cellules et y importent leurs propriétés physiques. Parmi ces nano-objets intelligents, les nano-aimants apportent des potentialités inédites : détectables, manipulables à distance, stimulables par un champ magnétique, ils peuvent être à la fois des nano-traceurs pour l’imagerie médicale, des nano-vecteurs pour transporter des agents thérapeutiques à leur cible, des nano-espions à l’intérieur des cellules, ou encore des nano-foyers pour brûler les cellules malignes. La maîtrise du magnétisme au cœur du vivant et de ces nano-robots multifonctions permet d’inventer de nouvelles solutions diagnostiques, thérapeutiques et réparatrices. Dans cet article, nous montrerons comment les nano-aimants peuvent être mis au service de nouvelles stratégies thérapeutiques qui reposent sur l’injection de cellules dans l’organisme : les thérapies cellulaires